Objective:To evaluate the efficacy and safety of telitacicept in the treatment of systemic lupus erythematosus (SLE) .Methods:The clinical data of 25 SLE patients who received standard therapy combined with telitacicept at the Department of Dermatology, Xiangya Second Hospital, Central South University, from 2021 to 2024 were retrospectively collected. Baseline demographic and clinical characteristics were analyzed. Changes in skin lesions, joint pain symptoms, complete blood count, and biochemical parameters at 4, 12, and 24 weeks of treatment were compared with baseline (week 0). The Wilcoxon signed-rank test was used to compare complement C3 and C4 levels before and after treatment, and univariate logistic regression analysis was performed to explore factors influencing the efficacy of telitacicept.Results:Among the 25 SLE patients, 3 were male (12.0%) and 22 were female (88.0%). Based on the SLE Disease Activity Index (SLEDAI) -2000 scores, 8 patients were mild, 13 were moderate, and 4 were severe. Of the 11 SLE patients with rashes before treatment, 6 achieved complete remission at 12 weeks. Among the 7 patients with joint pain before treatment, 4 experienced symptom resolution at 24 weeks. The proportion of patients with leukopenia at baseline and at 4, 12, and 24 weeks was 10/25 (40.0%), 0/24 (0), 1/22 (4.5%), and 2/19 (10.5%), respectively. The proportion of patients with thrombocytopenia was 6/25 (24.0%), 3/24 (12.5%), 1/22 (4.5%), and 1/19 (5.3%), respectively, and the proportion of patients with anemia was 7/25 (28.0%), 3/24 (12.5%), 1/22 (4.5%), and 1/19 (5.3%), respectively. At baseline, 11 out of 25 patients (44.0%) had proteinuria. At 12 weeks, the urinary protein quantification level (0.4 [0, 0.6] g/L) was significantly lower than at baseline (0.9 [0.8, 1.2] g/L). The SLE responder index-4 (SRI4) response rates at 4, 12, and 24 weeks were 14/18, 15/17, and 12/14, respectively. Complement C3 and C4 levels were significantly higher at 4, 12, and 24 weeks compared to baseline (all P < 0.001). Univariate logistic regression analysis showed that age, disease duration, glucocorticoid dosage, baseline complement C4 levels, antinuclear antibody titer, and SLEDAI-2K score did not significantly affect the efficacy of telitacicept (SRI4 response rate at 12 weeks) (all P > 0.05). No serious adverse reactions related to telitacicept were observed in patients. Conclusions:Telitacicept improved skin lesions, complement C3 and C4 levels, and anti-double-stranded DNA antibody levels in SLE patients. No association was found between the efficacy of telitacicept and baseline SLEDAI-2K scores, antinuclear antibody titers, or complement C4 levels, suggesting that telitacicept is an effective and safe treatment for SLE patients.

Objective:To evaluate the efficacy and safety of telitacicept in the treatment of systemic lupus erythematosus (SLE) .Methods:The clinical data of 25 SLE patients who received standard therapy combined with telitacicept at the Department of Dermatology, Xiangya Second Hospital, Central South University, from 2021 to 2024 were retrospectively collected. Baseline demographic and clinical characteristics were analyzed. Changes in skin lesions, joint pain symptoms, complete blood count, and biochemical parameters at 4, 12, and 24 weeks of treatment were compared with baseline (week 0). The Wilcoxon signed-rank test was used to compare complement C3 and C4 levels before and after treatment, and univariate logistic regression analysis was performed to explore factors influencing the efficacy of telitacicept.Results:Among the 25 SLE patients, 3 were male (12.0%) and 22 were female (88.0%). Based on the SLE Disease Activity Index (SLEDAI) -2000 scores, 8 patients were mild, 13 were moderate, and 4 were severe. Of the 11 SLE patients with rashes before treatment, 6 achieved complete remission at 12 weeks. Among the 7 patients with joint pain before treatment, 4 experienced symptom resolution at 24 weeks. The proportion of patients with leukopenia at baseline and at 4, 12, and 24 weeks was 10/25 (40.0%), 0/24 (0), 1/22 (4.5%), and 2/19 (10.5%), respectively. The proportion of patients with thrombocytopenia was 6/25 (24.0%), 3/24 (12.5%), 1/22 (4.5%), and 1/19 (5.3%), respectively, and the proportion of patients with anemia was 7/25 (28.0%), 3/24 (12.5%), 1/22 (4.5%), and 1/19 (5.3%), respectively. At baseline, 11 out of 25 patients (44.0%) had proteinuria. At 12 weeks, the urinary protein quantification level (0.4 [0, 0.6] g/L) was significantly lower than at baseline (0.9 [0.8, 1.2] g/L). The SLE responder index-4 (SRI4) response rates at 4, 12, and 24 weeks were 14/18, 15/17, and 12/14, respectively. Complement C3 and C4 levels were significantly higher at 4, 12, and 24 weeks compared to baseline (all P < 0.001). Univariate logistic regression analysis showed that age, disease duration, glucocorticoid dosage, baseline complement C4 levels, antinuclear antibody titer, and SLEDAI-2K score did not significantly affect the efficacy of telitacicept (SRI4 response rate at 12 weeks) (all P > 0.05). No serious adverse reactions related to telitacicept were observed in patients. Conclusions:Telitacicept improved skin lesions, complement C3 and C4 levels, and anti-double-stranded DNA antibody levels in SLE patients. No association was found between the efficacy of telitacicept and baseline SLEDAI-2K scores, antinuclear antibody titers, or complement C4 levels, suggesting that telitacicept is an effective and safe treatment for SLE patients.

Objective To evaluate the clinical efficacy and safety of anatomical repair and anatomical reconstruction through Meta-analysis.Methods Systematically search PubMed,Embase,Wanfang database,China National Knowledge Infrastructure and other databases were used to obtain the relevant literature in the treatment of chronic lateral instability of the ankle joint with anatomical repair and reconstruction from the establishment of each database to December 2022,and Revman 5.4 and R 4.2 software were used for Meta-analysis.Results Eight articles were finally included in this paper.All were randomized controlled trials.The results of Meta-analysis showed that:there were statistically significant differences between anatomical repair and anatomical reconstruction in the anterior talar translation (MD=0.54,95％CI:0.27-0.81,P<0.01),talus tilt angle (MD=0.36,95％CI:0.07-0.66,P=0.02),and American Orthopaedic Foot & Ankle Society scale (MD=-4.79,95％CI:-6.58--3.01,P<0.01),but there was no statistically significant difference in complications (RR=1.13,95％CI:0.32-3.97,P=0.85).Conclusion Anatomical reconstruction is superior to anatomical repair in clinical efficacy,while the risk of complications is comparable between two.

Objective To evaluate the protective effect of polysaccharide nucleic acid fraction of bacillus Calmette-Guerin (BCG-PSN) against atopic dermatitis (AD) in Nc/Nga mice,and to explore its possible mechanism.Methods Sixteen Nc/Nga mice were classified into normal control group (n =4),low-concentration BCG-PSN group (n=5) and high-concentration BCG-PSN group (n =7) to be subcutaneously injected with sodium chloride physiological solution,BCG-PSN of 0.1 mg/kg and 0.5 mg/kg respectively,at 1,8,15 and 22 days of age.Dinitrochlorobenzene (DNCB) was repeatedly and topically applied to these Nc/Nga mice to induce AD-like lesions at 49 days of age.The preventive effect of BCG-PSN against AD was evaluated by dermatitis scores,scratching frequency,histopathological manifestations and immunological parameters (including IgE,i nterleukin (IL)-4 and-12,and interferon (IFN)-γ).Results Repeated injection of BCG-PSN within 4 weeks after birth significantly decreased the severity of DNCB-induced AD-like lesions,dermatitis scores and scratching behavior in Nc/Nga mice.There was no statistical difference in scratching frequency between the high-and low-concentration BCG-PSN groups.BCG-PSN treatment reduced the plasma level of IgE in Nc/Nga mice in a dose-dependent manner.BCG-PSN at 0.5 mg/kg increased the number of cells secreting IFN-γ in skin lesions of mice.Both doses of BCG-PSN down-regulated IL-4 level,but up-regulated IL-12 level in the culture supernatant of spleen mononuclear cells from mice.Conclusion Early injection of BCG-PSN could protect Nc/Nga mice against dermatitis by promoting the proliferation of IFN-γ-secreting cells,increasing the synthesis of IL-12,and reducing the levels of IL-4 and IgE.

Objective To evaluate the efficacy and safety of total glucosides of paeony combined with ebastine for the treatment of chronic idiopathic urticaria.Methods A randomized,open-labeled,positive drugcontrolled,parallel-group study was carried out.Sixty patients with chronic idiopathic urticaria were randomly divided into two groups using a random digit table:combined group treated with total glucosides of paeony 600 mg thrice daily combined with ebastine 10 mg per day,control group treated with ebastine 10 mg per day only.The treatment lasted 12 weeks followed by a four-week follow-up.Adverse reactions were recorded and treatment efficacy was evaluated by using urticaria activity score over seven days (UAS7).Results The UAS7 was 9.28 ±4.59,5.83 ± 4.44 and 7.52 ± 5.57 in the combined group on week 8,12 after the initiation of treatment and week 4 after the withdrawal of treatment,respectively,significantly lower than that in the control group at the three time points (13.29 ± 4.72,P ＜ 0.05; 9.86 ± 5.46,P ＜ 0.01; 16.21 ± 5.34,P ＜ 0.01).Significant differences were observed in the response rate between the combined group and control group at the end of the 12-week treatment (75.9％ vs.42.9％,x2 =4.56,P ＜ 0.05).There was a decreased recurrence rate in the combined group combined with the control group at the end of the follow-up (13.6％ vs.50.0％,x2 =3.90,P ＜0.05).No obvious adverse reactions were noted in either of the two groups.Conclusion Total glucosides of paeony could markedly enhance the efficacy of ebastine for the treatment of chronic idiopathic urticaria with a reduction in recurrence rate.

ObjectiveTo observe the effects of hypoxia inducible factor-1 alpha (HIF-1α)-targeting small interfering RNA(siRNA) on the expression of HIF-1α and vascular endothelial growth factor (VEGF) in HaCaT ceils under hypoxic conditions. MethodsHaCaT cells were cultured and divided into four groups, normal control group (without any treatment), hypoxia group (cultured under hypoxic conditions for 24 hours),liposome control group (transfected with liposome followed by hypoxic culture for 24 hours), RNA interference group (transfected with HIF-1α-targeting siRNA/liposome complexes followed by hypoxic culture for 24 hours). Fluorescence real-time quantitative PCR was utilized to determine HIF-1oα and VEGF mRNA expression in HaCaT cells, and Western blot to detect HIF-1α and VEGF protein expression. ResultsNo significant difference was observed in the mRNA expression of HIF-1α between the hypoxia group and normal control group(0.907 ± 0.032 vs. 0.878 ± 0.034, F =1.108, P ＞ 0.05), while the expression levels of VEGF mRNA,HIF-1α and VEGF proteins were significantly higher in the hypoxia group than in the normal control group (0.935 ± 0.032 vs. 0.652 ± 0.053, 0.813 ± 0.047 vs. 0.236 ± 0.014, 0.791 ± 0.030 vs. 0.316 ± 0.013, all P ＜0.05). A significant decline was noted in the mRNA and protein expression levels of VEGF (0.230 ± 0.044 vs.0.978 ± 0.030, 0.213 ± 0.026 vs. 0.817 ± 0.049, both P ＜ 0.05) and HIF-1α(0.497 ± 0.033 vs. 0.806 ±0.040, 0.249 ± 0.028 vs. 0.833 ± 0.052, both P ＜ 0.05) in the RNA interference group than in the liposome control group. ConclusionsHypoxia may enhance the expression of HIF-1α and VEGF in HaCaT cells, and to inhibit the HIF-1α expression may suppress the expression of VEGF in HaCaT cells under hypoxia.

OBJECTIVE: To observe the effect of hypoxia inducible factor -1α (HIF-1α) small interfering RNA (siRNA) on the expression of HIF-1α and inducible nitric oxide synthase (iNOS) in HaCaT cells under hypoxia. METHODS: HaCaT cells were divided into 4 groups: the normal control group (without any treatment), the hypoxia group (under hypoxia for 24 h), the liposome control group (HaCaT cells transfected with liposome before hypoxia treatment), the RNA interference group (HaCaT cells transfected with siRNA sequences then under hypoxia for 24 h). Real-time PCR and Western blot were utilized to determine HIF-1α and iNOS mRNA and protein expression in HaCaT cells. RESULTS: There was no significant difference of the mRNA expression of HIF-1α between the hypoxia group and the normoxia group (P>0.05), but the protein expressions of HIF-1α was increased in the hypoxic group than that in the normoxia group (P<0.05). Both the mRNA and protein expression of iNOS were increased in hypoxic conditions than that in the normoxia (P<0.05). Decreases were more significant in the mRNA and protein expression of HIF-1α and iNOS in the RNA interference group than that in the liposome control group in HaCaT cells (P<0.05). CONCLUSION Hypoxia increased HIF-1α and iNOS expression in HaCaT cells and inhibition of HIF-1α expression decreased iNOS expression.
Cell Hypoxia ; Cell Line ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; genetics ; metabolism ; Keratinocytes ; cytology ; metabolism ; Nitric Oxide Synthase Type II ; genetics ; metabolism ; RNA Interference ; RNA, Messenger ; genetics ; metabolism ; RNA, Small Interfering ; genetics

Objective To investigate the effect of TGF-β1/SMAD signaling pathway on K562 cells growth inhibition caused by HMBA. Methods After establishing the in vitro differentiation model with HMBA on K562 cells, the MTT assay was used to detect the proliferation of K562 cells, the cell cycle profile was detected by flow cytometry, and the mRNA expression of TGF-β1, SMAD3, SMAD4 and EVI1 was measured by RT-PCR assay. Results HMBA could inhibit the proliferation and promote the differentiation of K562 cells obviously, which was time and concentration-dependent, and the 72 h corresponding IC50, was about 2 mmol/L. Within 72 h, flow cytometry assay indicated that the ration of G0-G1 phase cells was up-regulated, and the results of RT-PCR showed that relative mRNA expression of TGF-β1, SMAD3 and SMAD4 at mRNA level was increased gradually while that of EVI1 was decreased gradually. Conclusion HMBA can inhibit K562 cells proliferation through TGF-β1/SMAD signaling pathway.

Objective To determine the effect of bacille Calmette-Guerin-polysaccharide nucleic acid (BCG/PSN)on 2,4-dinitrochlorobenzene(DNCB)-induced atopic dermatitis-like skin lesions in Nc/Nga mice.Methods Fifteen mice were randomly and equally classified into 3 groups,i.e.,control group receiving topical acetone on foot pad and abdomen and intraperitoneal injection of physiological saline,model group receiving topical 5% DNCB solution and intraperitoneal injection of physiological saline,treatment group receiving 5% DNCB solution and intraperitoneal iniection of BCG/PSN,and all drugs were used every other day for 7 weeks.Further more,0.1% DNCB was topically applied on the ear and neck of Nc/Nga mice once a week from week 2 to week 7.The effects of BCG/PSN were evaluated by ear thickness,skin histopathology and immunological parameters.Results Repeated application of DNCB caused the development of eczematous dermatitis in mice.Mice in model group chnieally manifested skin dryness,erythema,edema and erosion with histopathological changes including dermal and epidermal thickening,hyperkeratosis,and inflammatory infiltration.The serum levels of IL-4 and IrE in model group were significantly higher than those in control group[(174.72±12.64)μg/L vs (17.32±3.56)μg/L,(91.49±6.32)ng/L vs (83.95±6.63)ng/L,both P<0.05].Increased serum IL-12 and IFN-γ and decreased serum IgE were observed in treatment group compared with the model group[(122.10±4.64)ng/L vs (20.14±6.15)ng/L(73.89±2.39)ng/L vs (51.53±3.45)ng/L, (84.27±9.35)μg/L vs (174.72±12.64)μg/L, all P<0.05].Conclusion BCG/PSN might be beneficial for the treatment of atopie dermatitis-like skin lesions in Nc/Nga mice by enhancing the secretion of IL-12 and IFN-γ and suppressing the synthesis of IgE.

Objective To evaluate the positive effects of cisplatin on sensitivity of human glioma U251 to tumor necrosis factor-related apoptosis inducing ligand and to investigate the potential mechanism. Methods The expression of green fluorescent protein (GFP) in U251 which was transfected with pAdxsi-GFP-TRAIL was observed by inverted fluorescent microscope ×400) and to ascertain the MOI. The proliferation inhibition was studied by MTT method. Morphological change was detected through inverted florescent microscope and the Hoechst33342 staining assay was used to verify whether cell apoptosis could be induced or not. The cell apoptosis was also analyzed by flow cvtometry with propidium iodide staining. Semi-quantitative RT-PCR was introduced to detect the mRNA expression of apoptosis related gene.Results The expression of TRAIL mRN A was significantly upregulated after transfection. Compared with treatment group of cisplatin and TRAIL alone, the proliferation of U2S1 was significantly inhibited in the cisplatin sensitizing TRAIL group (P < 0.05 ). Nuclear shrinkage and pyknosis fragmentation were observed by Hoechst 33342 staining assay; Apoptotic peak was detected from the results of flow cvtometry and there were significant differences between the sensitizing group and the other two groups ( P < 0.05 ) ; Moreover, the relatively high expression of TRAIL, DR5, caspaseS and down - regulated survivin genes were also observed. There was no significant changes in DR4 expression. Conclusion Cisplatin could extremely enhance the sensitivity of U251 cells to TRAIL And the potential mechanism may related to the increase of TRAIL, DRS, caspaseS genes while the reduction of surivivin gene.